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I am a clinical and health services investigator whose primary interest is in improving the quality of end-stage renal disease (ESRD) care among older adults. My previous and current work aims to describe outcomes (especially geriatric outcomes) in older patients and to compare the effectiveness of different ESRD management strategies on these outcomes.

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Abstract

It is often difficult to synthesize information about the risks and benefits of recommended management strategies in older patients with end-stage renal disease since they may have more comorbidity and lower life expectancy than patients described in clinical trials or practice guidelines. In this review, we outline a framework for individualizing end-stage renal disease management decisions in older patients. The framework considers three factors: life expectancy, the risks and benefits of competing treatment strategies, and patient preferences. We illustrate the use of this framework by applying it to three key end-stage renal disease decisions in older patients with varying life expectancy: choice of dialysis modality, choice of vascular access for hemodialysis, and referral for kidney transplantation. In several instances, this approach might provide support for treatment decisions that directly contradict available practice guidelines, illustrating circumstances when strict application of guidelines may be inappropriate for certain patients. By combining quantitative estimates of benefits and harms with qualitative assessments of patient preferences, clinicians may be better able to tailor treatment recommendations to individual older patients, thereby improving the overall quality of end-stage renal disease care.

Abstract

An increasing number of older adults are being treated for end-stage renal disease (ESRD) with long-term dialysis.To determine how ESRD treatment practices for older adults vary across regions with differing end-of-life intensity of care.Retrospective observational study using a national ESRD registry to identify a cohort of 41,420 adults (of white or black race), aged 65 years or older, who started long-term dialysis or received a kidney transplant between June 1, 2005, and May 31, 2006. Regional end-of-life intensity of care was defined using an index from the Dartmouth Atlas of Healthcare.Incidence of treated ESRD (dialysis or transplant), preparedness for ESRD (under the care of a nephrologist, having a fistula [vs graft or catheter] at time of hemodialysis initiation), and end-of-life care practices.Among whites, the incidence of ESRD was progressively higher in regions with greater intensity of care and this trend was most pronounced at older ages. Among blacks, a similar relationship was present only at advanced ages (men aged > or = 80 years and women aged > or = 85 years). Patients living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to be under the care of a nephrologist before the onset of ESRD (62.3% [95% confidence interval {CI}, 61.3%-63.3%] vs 71.1% [95% CI, 69.9%-72.2%], respectively) and less likely to have a fistula (vs graft or catheter) at the time of hemodialysis initiation (11.2% [95% CI, 10.6%-11.8%] vs 16.9% [95% CI, 15.9%-17.8%]). Among patients who died within 2 years of ESRD onset (n = 21,190), those living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to have discontinued dialysis before death (22.2% [95% CI, 21.1%-23.4%] vs 44.3% [95% CI, 42.5%-46.1%], respectively), less likely to have received hospice care (20.7% [95% CI, 19.5%-21.9%] vs 33.5% [95% CI, 31.7%-35.4%]), and more likely to have died in the hospital (67.8% [95% CI, 66.5%-69.1%] vs 50.3% [95% CI, 48.5%-52.1%]). These differences persisted in adjusted analyses.There are pronounced regional differences in treatment practices for ESRD in older adults that are not explained by differences in patient characteristics.

Abstract

It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.

Abstract

The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level.To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis.Observational study.U.S. Renal Data System, a comprehensive, national registry of patients with ESRD.Octogenarians and nonagenarians initiating dialysis between 1996 and 2003.Rates of dialysis initiation and survival.The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions.Survival of patients with incident ESRD who did not begin dialysis could not be assessed.The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly.

Abstract

Patients with end-stage renal disease report infrequent end-of-life discussions, and nephrology trainees report feeling unprepared for end-of-life decision making, but the views of dialysis medical directors have not been studied.Our objective is to understand dialysis medical directors' views and practice patterns on end-of-life decision making for patients with ESRD.We administered questionnaires to dialysis medical directors during medical director meetings of three different dialysis organizations in 2013. Survey questions corresponded to recommendations from the Renal Physicians Association clinical practice guidelines on initiation and withdrawal of dialysis.There were 121 medical director respondents from 28 states.The majority of respondents felt "very prepared" (66%) or "somewhat prepared" (29%) to participate in end-of-life decisions and most (80%) endorsed a model of shared decision making. If asked to do so, 70% of the respondents provided prognostic information "often" or "nearly always." For patients with a poor prognosis, 36% of respondents would offer a time-limited trial of dialysis "often" or "nearly always", while 56% of respondents would suggest withdrawal from dialysis "often" or "nearly always" for those with a poor prognosis currently receiving dialysis therapy. Patient resistance and fear of taking away hope were the most commonly cited barriers to end-of-life discussions.Views and reported practice patterns of medical directors are consistent with clinical practice guidelines for end-of-life decision making for patients with end-stage renal disease but inconsistent with patient perceptions.

Abstract

This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60?mL/minute/1.73?m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7?mL/min/1.73?m) were more likely to have had menopause before age 45 years (26% vs 23%, P?=?0.02) but were less likely to experience VMS (38% vs 46%, P?0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction?=?0.53), coronary heart disease (Pinteraction?=?0.12), or stroke (Pinteraction?=?0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

Abstract

The term "nondisease-specific" has been used to describe problems that cross multiple domains of health and are not necessarily the result of a single underlying disease. Although individuals with reduced eGFR and elevated albumin-to-creatinine ratio have many comorbidities, the prevalence of and outcomes associated with nondisease-specific problems have not been well studied.Participants included 3557 black and white United States adults ?75 years of age from the Reasons for Geographic and Racial Differences in Stroke Study. Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Hazard ratios for mortality over a median (interquartile range) of 5.4 (4.2-6.9) years of follow-up associated with one, two, or three to six nondisease-specific problems were calculated and stratified by eGFR (?60, 45-59, and <45 ml/min per 1.73 m(2)) and separately, albumin-to-creatinine ratio (<30, 30-299, and ?300 mg/g). Secondary outcomes included hospitalizations and emergency department visits over 1.8 (0.7-4.0) and 2.3 (0.9-4.7) years of follow-up, respectively.The prevalence of nondisease-specific problems was more common at lower eGFR and higher albumin-to-creatinine ratio levels. Within each eGFR and albumin-to-creatinine ratio strata, the risk for mortality was higher among those with a greater number of nondisease-specific problems. For example, among those with an eGFR=45-59 ml/min per 1.73 m(2), the multivariable adjusted hazard ratios (95% confidence intervals) for mortality associated with one, two, or three to six nondisease-specific problems were 1.17 (0.78 to 1.76), 1.95 (1.24 to 3.07), and 2.44 (1.39 to 4.27; P trend <0.001). Risk for hospitalization and emergency department visits was higher among those with more nondisease-specific problems within eGFR and albumin-to-creatinine ratio strata.Among older adults, nondisease-specific problems commonly co-occur with reduced eGFR and elevated albumin-to-creatinine ratio. Identification of nondisease-specific problems may provide mortality risk information independent of measures of kidney function.

Abstract

Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ?67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ?9 or an hospice eligibility criteria ?3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.

Abstract

Although dialysis prolongs life for patients with end-stage kidney disease, 20% of deaths in this population are preceded by dialysis therapy withdrawal. Recently, there has been more focus on conservative (nondialytic) care as a legitimate option, particularly for elderly patients. This study aims to describe patients' and caregivers' perspectives on conservative treatment and end-of-life care in chronic kidney disease (CKD).Systematic review and thematic synthesis of qualitative studies.Patients with CKD and caregivers.MEDLINE, Embase, PsycINFO, CINAHL, and reference lists were searched to May 2013.Thematic synthesis was used to analyze the findings.26 studies involving more than 711 patients (non-dialysis dependent [n=41], hemodialysis [n=544], peritoneal dialysis [n=9]; unspecified dialysis modality [n=31], conservative management [n=86]) and 178 caregivers were included. We identified 5 themes: invasive suffering (bodily deterioration, loss of freedom and independence, unyielding fatigue and pain, resignation, treatment burden and harm, financial strain), personal vulnerability (imminence of death, misunderstanding and judgment, autonomy and dignity, medical abandonment, trust and safety), relational responsibility (being a burden, demonstrating loyalty, protecting others from grief), negotiating existential tensions (accepting natural course of life, disrupted aging, worthlessness, living on borrowed time, respecting sanctity of life, life satisfaction, preserving self-identity), and preparedness (decisional clarity, informational power, spirituality and hope).Non-English articles were excluded; therefore, the transferability of findings to other populations is unclear.Some patients with CKD experience physical and psychosocial frailty and feel ambivalent about prolonging life. Some caregivers believe in providing relief from suffering, but are uncertain about making decisions regarding dialysis therapy initiation and discontinuation. We suggest that CKD management should encompass palliative care strategies that promote emotional resilience, sense of well-being, and self-value. Also, respectful and attentive communication may empower patients to convey their values and preferences about their own care.

Abstract

Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers.In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared.In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02).Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

Abstract

Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.Level of estimated glomerular filtration rate (eGFR) and proteinuria.Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ? 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ? 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.

Abstract

Preparation for end-stage renal disease (ESRD) is widely acknowledged to be suboptimal in the United States. We sought to determine whether participation in a kidney disease screening and education program resulted in improved ESRD preparation and survival in 595 adults who developed ESRD after participating in the National Kidney Foundation Kidney Early Evaluation Program (KEEP), a community-based screening and education program. Non-KEEP patients were selected from a national ESRD registry and matched to KEEP participants based on demographic and clinical characteristics. The main outcomes were pre-ESRD nephrologist care, placement of permanent vascular access, use of peritoneal dialysis, pre-emptive transplant wait listing, transplantation, and mortality after ESRD. Participation in KEEP was associated with significantly higher rates of pre-ESRD nephrologist care (76.0% vs. 69.3%), peritoneal dialysis (10.3% vs. 6.4%), pre-emptive transplant wait listing (24.2% vs. 17.1%), and transplantation (9.7% vs. 6.4%) but not with higher rates of permanent vascular access (23.4% vs. 20.1%). Participation in KEEP was associated with a lower risk for mortality (hazard ratio 0.80), but this was not statistically significant after adjusting for ESRD preparation. Thus, participation in a voluntary community kidney disease screening and education program was associated with higher rates of ESRD preparation and survival.

Abstract

Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

Abstract

Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

Abstract

Frailty is a physiologic state of increased vulnerability to stressors that results from decreased physiologic reserves or dysregulation of multiple physiologic systems. The construct of frailty has been operationalized as a composite of poor physical function, exhaustion, low physical activity, and weight loss. Several studies have now examined the prevalence of frailty among chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients and have found frailty to be more common among individuals with CKD than among those without. Furthermore, frailty is associated with adverse outcomes among incident dialysis patients, including higher risk of hospitalization and death. Recent evidence shows that frail patients are started on dialysis earlier (at a higher estimated glomerular filtration rate [eGFR]) on average than nonfrail patients, but it remains unclear whether these patients' frailty is a result of uremia or is independent of CKD. The survival disadvantage that has been associated with early initiation of dialysis in observational studies could be mediated in part through confounding on the basis of unmeasured frailty. However, available data do not suggest improvement in frailty upon initiation of dialysis; rather, the trajectory appears to be toward higher levels of dependence in activities of daily living (ADLs) after dialysis initiation. Overall, there are no data to suggest that frail patients derive any benefit from early initiation of dialysis either in the form of improved survival or functional status.

Abstract

Among patients receiving maintenance dialysis, weight loss at any body mass index is associated with mortality. However, it is not known whether weight changes before dialysis initiation are associated with mortality and if so, what risks are associated with weight gain or loss.Linking data from the US Renal Data System to a national registry of nursing home residents, this study identified 11,090 patients who started dialysis between January of 2000 and December of 2006. Patients were categorized according to weight measured between 3 and 6 months before dialysis initiation and the percentage change in body weight before dialysis initiation (divided into quintiles). The outcome was mortality within 1 year of starting dialysis.There were 361 patients (3.3%) who were underweight (Quételet's [body mass] index<18.5 kg/m(2)) and 4046 patients (36.5%) who were obese (body mass index ? 30 kg/m(2)) before dialysis initiation. The median percentage change in body weight before dialysis initiation was -6% (interquartile range=-13% to 1%). There were 6063 deaths (54.7%) over 1 year of follow-up. Compared with patients with minimal weight changes (-3% to 3%, quintile 4), patients with weight loss ? 15% (quintile 1) had 35% higher risk for mortality (95% confidence interval, 1.25 to 1.47), whereas those patients with weight gain ? 4% (quintile 5) had a 24% higher risk for mortality (95% confidence interval, 1.14 to 1.35) adjusted for baseline body mass index and other confounders.Among nursing home residents, changes in body weight in advance of dialysis initiation are associated with significantly higher 1-year mortality.

Five Policies to Promote Palliative Care for Patients with ESRDCLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGYTamura, M. K., Meier, D. E.2013; 8 (10): 1783-1790

Abstract

Patients with ESRD experience complex and costly care that does not always meet their needs. Palliative care, which focuses on improving quality of life and relieving suffering for patients with serious illnesses, could address a large unmet need among patients with ESRD. Strengthening palliative care is a top policy priority for health reform efforts based on strong evidence that palliative care improves value. This commentary outlines palliative care policies for patients with ESRD and is directed at policymakers, dialysis providers, nephrology professional societies, accreditation organizations, and funding agencies who play a key role in the delivery and determination of quality of ESRD care. Herein we suggest policies to promote palliative care for patients with ESRD by addressing key barriers, including the lack of access to palliative care, lack of capacity to deliver palliative care, and a limited evidence base. We also provide examples of how these policies could be implemented within the existing ESRD care infrastructure.

Abstract

Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD.This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ? 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death.During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure.In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.

Abstract

Cognitive impairment is common in patients with end-stage renal disease receiving hemodialysis 3 times per week.Randomized clinical trial.218 individuals participating in the Frequent Hemodialysis Network (FHN) Daily Trial and 81 participating in the FHN Nocturnal Trial.The Daily Trial tested in-center hemodialysis 6 times per week versus 3 times per week. The Nocturnal Trial tested home nocturnal hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per week.Cognitive function was measured at baseline, month 4, and month 12. The primary outcome was performance on the Trail-Making Test, Form B, a measure of executive function, and a secondary outcome was performance on the Modified Mini-Mental State Examination, a measure of global cognition. The domains of attention, psychomotor speed, memory, and verbal fluency were assessed in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial.We found no benefit of frequent hemodialysis in either trial for the primary cognitive outcome (Daily Trial: OR for improvement, 0.99; 95% CI, 0.59-1.66; Nocturnal Trial: OR, 1.19; 95% CI, 0.48-2.96). Similarly, there was no benefit of frequent hemodialysis in either trial on global cognition, the secondary cognitive outcome. Exploratory analyses in the Daily Trial suggested possible benefits of frequent hemodialysis for memory and verbal fluency, but not for attention and psychomotor speed. Exploratory analyses in the Nocturnal Trial suggested no benefit of frequent hemodialysis on attention, psychomotor speed, memory, or verbal fluency.Unblinded intervention, small sample.Frequent hemodialysis did not improve executive function or global cognition.

Abstract

Many older patients with advanced CKD approaching ESRD do not receive timely nephrology care, although data suggest that the situation may be improving. In 2005-2008, 43% of older patients who initiated renal replacement therapy had experienced an outpatient nephrologist consultation more than 1 year before starting treatment. Earlier consultation with a nephrologist has been found to provide better access to peritoneal dialysis and kidney transplantation, better preparation for the chosen dialytic modality, and improved survival after start of dialysis or receipt of a kidney transplant. Recent data suggest that older individuals are less likely to receive treatment for ESRD compared with younger individuals in whom almost all receive dialysis treatment or transplantation. Little is known about the role nephrologists play in the decision whether to initiate dialysis or choose a conservative route among older adults with ESRD. Defining the appropriate role and involvement of nephrologists in the decision about initiating renal replacement therapy in older adults seems ripe for further investigation and discussion.

Abstract

The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ? 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03-5.92) and IADL impairment (OR 3.86, 95% CI 1.60-9.28).Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.

Abstract

Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System.Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P

Abstract

Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.Cross-sectional analysis.Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.Depressive symptoms measured by Beck Depression Inventory (BDI).Demographic and clinical factors.Elevated depressive symptoms (BDI score ?11) and antidepressant medication use.Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ?60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

Timing of initiation of dialysis: time for a new direction?CURRENT OPINION IN NEPHROLOGY AND HYPERTENSIONAbra, G., Tamura, M. K.2012; 21 (3): 329-333

Abstract

The past 15 years have seen tremendous growth in the initiation of dialysis at higher levels of kidney function in the setting of mixed evidence and at great societal economic cost. We review recent data on the early dialysis initiation trend, the clinical and economic impact of early dialysis initiation and the future implications for the management of advanced chronic kidney disease (CKD).The percentage of patients who initiate dialysis with an estimated glomerular filtration rate (eGFR) above 10 ?ml/min/1.73m(2) is now greater than 50%, including 20% who initiate with an eGFR above 15 ml/min/1.73m(2). The drivers behind these findings are probably diverse but recent literature does not seem to support a higher symptom burden among the ageing CKD population as the major cause. The Initiating Dialysis Early And Late (IDEAL) trial provides guidance on the safety of waiting for symptoms or lower levels of estimated glomerular filtration rate prior to beginning dialysis. In addition, economic analyses based on the IDEAL and US Renal Data System findings suggest that significant cost savings could be achieved by reversing the early initiation trend.These findings should help clinicians and policy makers looking to rein in costs while maintaining the quality of CKD care.

Abstract

Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ? 150 or DBP ? 90 mm Hg).The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ? 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ? 150 mm Hg or DBP ? 90 mm Hg), mostly due to isolated systolic hypertension (54%).In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.

Abstract

Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.Between June 2005 and June 2007, CDS collected data on self-reported physical activity, nutrition, and health-related quality of life from patients starting dialysis in 296 facilities located throughout the United States. Baseline serum samples were collected from participants in a nutrition sub-study of CDS.Serum albumin and prealbumin were measured as markers of nutrition, and C-reactive protein (CRP) and ?-1-acid glycoprotein as markers of inflammation. Self-reported physical activity was characterized by the maximum activity score (MAS) and adjusted activity score (AAS) of the Human Activity Profile.The mean age of participants in the analytic cohort (n = 201) was 61 years. The MAS and AAS were below the 10th and first percentile, respectively, in comparison with healthy 60 year-old norms. Both activity scores were directly correlated with albumin (r(2) = 0.3, P < .0001) and prealbumin (r(2) = 0.3, P < .0001), and inversely correlated with CRP (AAS: r(2) = -0.2, P = .01; MAS: r(2) = -0.1, P = .08). In multivariate analyses adjusting for age, gender, race/ethnicity, diabetes status, and center, both activity scores were directly correlated with prealbumin and inversely correlated with CRP.Patients new to dialysis with laboratory-based evidence of malnutrition and/or inflammation are likely to report lower levels of physical activity.

Abstract

As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ? 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.

Abstract

Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown.Prospective cohort study.A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study.Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.Incident cognitive impairment was defined as score ?4 on the 6-Item Screener at the last follow-up visit.During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ?300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR ?60 mL/min/1.73 m(2), eGFR <60 mL/min/1.73 m(2) was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m(2) was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend).Single measures of albuminuria and eGFR, screening test of cognition.When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.

Abstract

Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70-79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73 m(2) 0.92, 95% confidence interval 0.87-0.98) and CKD (1.41, 1.04-1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.

Abstract

Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.

Abstract

Recent reports have suggested a close relationship between education and health, including mortality, in the United States.Observational cohort.We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP).Self-reported educational attainment.Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality.We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression.Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school.Lack of income data does not allow us to disentangle the independent effects of education from income.In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups.

Abstract

The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m(2). Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 14.3% compared with 16.8% using eGFR(MDRD). Using eGFR(CKD-EPI), 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m(2) using both equations, those with eGFR(CKD-EPI) of 60-89 mL/min/1.73 m(2) had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.

Abstract

Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.In this cross-sectional study, we used data collected from 2000-2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.Of 26,213 participants with CKD based on GFR estimated using the MRDR equation (eGFR(MDRD)), 23,572 (90%) also were classified with CKD based on eGFR(CKD-EPI). Based on eGFR(MDRD), 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with stages 1-5, respectively. Based on eGFR(CKD-EPI), 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with stages 1-5, respectively. Reclassification to a less advanced CKD stage using eGFR(CKD-EPI) was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFR(CKD-EPI).Using eGFR(CKD-EPI) led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.

Abstract

Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown.This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations.CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14).Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.

Abstract

Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

Abstract

Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment.

Abstract

End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important.The aim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials.In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients' self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden.Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.

Abstract

Factors driving the trend of earlier dialysis initiation for persons with end-stage renal disease are unknown. We wanted to determine the association of the number and type of signs and symptoms with timing of initiation of dialysis in US nursing home residents.Observational study.We used data from the US Renal Data System linked with the Minimum Data Set, a national registry of nursing home residents. The cohort consisted of 2,402 nursing home residents who initiated dialysis between 1998 and 2000 and had at least 2 recorded clinical assessments in the year before dialysis initiation.We evaluated 7 clinical signs and symptoms: dependence in activities of daily living, cognitive function, edema, dyspnea, nutritional problems, vomiting, and body size.Earlier dialysis initiation was defined as estimated glomerular filtration rate ? 1 5 mL/min/1.73 m² at the start of dialysis.Median estimated glomerular filtration rate at the start of dialysis was 9.8 (25th-75th percentile, 7.4-13.4) mL/min/1.73 m². After adjustment for age, sex, race, and comorbid conditions, each additional sign or symptom was associated with a higher odds for earlier dialysis initiation (OR, 1.16 per symptom; 95% CI, 1.06-1.28), as was each adversely changing sign or symptom (OR, 1.26 per symptom; 95% CI, 1.16-1.38). The population-attributable risk for earlier dialysis initiation associated with having one or more signs and symptoms of volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss was 31%; volume overload had the largest aggregate population-attributable risk.We lacked information about metabolic indications for dialysis initiation.Volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss were associated with earlier dialysis initiation; however, these factors explained less than one-third of cases of earlier dialysis initiation in nursing home residents.

Abstract

There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults.We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women).The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ?2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ?2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94-2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race.Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment.

Should there be an expanded role for palliative care in end-stage renal disease?CURRENT OPINION IN NEPHROLOGY AND HYPERTENSIONTamura, M. K., Cohen, L. M.2010; 19 (6): 556-560

Abstract

In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation.Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently. Furthermore, although hospice care is associated with improved symptom control and lower healthcare costs at the end of life, it is underutilized by the ESRD population, even among patients who withdraw from dialysis. A palliative care model incorporating communication of prognosis, advance care planning, symptom assessment and management, and timely hospice referral may improve quality of life and quality of dying. Resources and clinical practice guidelines are available to assist practitioners with incorporating palliative care into ESRD management.There is a large unmet need to alleviate the physical, psychosocial, and existential suffering of patients with ESRD. More fully integrating palliative care into ESRD management by improving end-of-life care training, eliminating structural and financial barriers to hospice use, and identifying optimal methods to deliver palliative care are necessary if we are to successfully address the needs of an aging ESRD population.

Abstract

Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications.Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors.Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors.

Abstract

Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

Abstract

To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors.Cross-sectional.Chronic Renal Insufficiency Cohort Study.Eight hundred twenty-five adults aged 55 and older with CKD.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean).Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P

Abstract

Rates of dialysis withdrawal are higher among the elderly and lower among Blacks, yet it is unknown whether preferences for withdrawal and engagement in advance care planning also vary by age and race or ethnicity. DESIGN, SETTING, PARTICIPANTS AND METHODS: We recruited 61 participants from two dialysis clinics to complete questionnaires regarding dialysis withdrawal preferences in five different health states. Engagement in advance care planning (end-of-life discussions), completion of advance directives and 'do not resuscitate' or 'do not intubate' (DNR/DNI) orders were ascertained by a questionnaire and from dialysis unit records.The mean age was 62 +/- 15 years; 38% were Black, 11% were Latino, 34% were White and 16% of participants were Asian. Blacks were less likely to prefer dialysis withdrawal as compared with Whites (odds ratio 0.16, 95% confidence interval 0.03-0.88) and other race/ethnicity groups, and this difference was not explained by age, education, comorbidity and other confounders. In contrast, older age was not associated with preferences for withdrawal. Rates of engagement in end-of-life discussions were higher than for documentation of advance care planning for all age and most race/ethnicity groups. Although younger participants and minorities were generally less likely to document treatment preferences as compared with older patients and Whites, they were not less likely to engage in end-of-life discussions.Preferences for withdrawal vary by race/ ethnicity, whereas the pattern of engagement in advance care planning varies by age and race/ethnicity. Knowledge of these differences may be useful for improving communication about end-of-life preferences and in implementing effective advance care planning strategies among diverse haemodialysis patients.

Abstract

Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive.

Abstract

The elderly constitute a substantial and growing fraction of the end-stage renal disease (ESRD) population. We review recent studies on ESRD incidence, management, and outcomes in the elderly.Rates of treated ESRD among the elderly (>80 years) have risen by more than 50% in the last decade. In studies with a large number of elderly patients, median survival after dialysis initiation is modest, and although a majority have reasonable life expectancy, a substantial minority of elderly patients experience very high early mortality rates after dialysis initiation. Quality of life results are mixed--compared with younger ESRD patients or non-ESRD elderly, mental well being is similar and physical well being is reduced in elderly patients with ESRD. In several studies, elderly patients with ESRD initiating peritoneal dialysis had higher mortality rates than elderly patients with ESRD initiating hemodialysis. Strategies such as nondialytic management of ESRD or dietary protein restriction and delayed dialysis initiation may be alternatives for elderly patients wishing to avoid dialysis initiation, but further studies are needed to determine the patients best suited for these approaches. Quality improvement initiatives in geriatric ESRD care have been successfully implemented in some centers and may ultimately improve care for elderly patients with ESRD.These findings should help to clarify some of the risks and benefits of dialysis in the elderly and may be useful in dialysis decision-making and management.

Abstract

The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity.Cross-sectional.23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample.Estimated glomerular filtration rate (eGFR).Cognitive impairment.Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m(2). Kidney function was analyzed in 10-mL/min/1.73 m(2) increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment.CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m(2) decrease in eGFR less than 60 mL/min/1.73 m(2) was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m(2) or greater.Longitudinal measures of cognitive function were not available.In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD.

Abstract

To assess the association between kidney function and change in body composition in older individuals.Prospective cohort study.Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee.Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study.Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis.High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07+/-0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05+/-0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19+/-0.04 kg/y per SD, P

Abstract

Recent studies suggest a high prevalence of cognitive impairment and dementia in persons with end-stage renal disease (ESRD), yet risk factors for dementia and its prognostic significance in persons with ESRD remain unclear. The goals of this study were to determine the prevalence, correlates and dialysis-related outcomes of dementia in an international sample of haemodialysis patients.We analysed data collected from a cohort of 16 694 patients in the Dialysis Outcomes and Practice Patterns Study. Dementia was defined as a diagnosis of dementia documented in the medical record. We used logistic regression to determine the baseline correlates of dementia and Cox proportional hazards models to determine the relative risk (RR) of death and dialysis withdrawal for patients with dementia, while adjusting for a number of confounding factors.Overall, 4% of the cohort had a recorded diagnosis of dementia. In the cross-sectional analyses, risk factors for dementia in the general population including age, black race, low educational attainment, cerebrovascular disease and diabetes, as well as modifiable uraemia-related factors, including markers of malnutrition and anaemia, were independently associated with dementia. After adjustment for a number of confounding factors, dementia was associated with an increased risk of death [RR 1.48, 95% confidence interval (CI) 1.32-1.66] and dialysis withdrawal (RR 2.01, 95% CI 1.57-2.57).Dementia is associated with adverse outcomes among ESRD patients. Dialysis providers should consider instituting routine screening for cognitive impairment among elderly patients in order to identify those at risk for associated adverse outcomes.

Abstract

The importance of hemodialysis session length relative to small solute (e.g., urea) clearance has been debated for many years. Longer session length augments clearance of larger molecules and may facilitate ultrafiltration; however, the independent effects of session length on survival and other outcomes are unknown. In this report, we review two recently published observational studies examining the association between hemodialysis session length and survival. Prospective clinical trials will be required to resolve the debate.

Abstract

The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease.A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors.The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

Abstract

To study the levels of systemic markers for inflammation with parameters of periodontal diseases in older people.A cross-sectional study was conducted in a cohort that is being followed prospectively on the effects of aging and body composition on morbidity.University of Pittsburgh, Pittsburgh, and University of Tennessee, Memphis.One thousand one hundred thirty-one participants (mean age+/-standard deviation 72.7+/-2.8); 66% white and 50% male.Periodontal examination, including probing depth and attachment loss, was performed. Periodontal disease extent was divided into 0% of sites with probing depth of 6 mm or more, 1% to 10% of sites with probing depth of 6 mm or more and more than 10% of sites with probing depth of 6 mm or more. Subgingival plaque samples were collected from four molar teeth, and the levels of periodontal pathogens were determined using the benzoyl-DL-arginine-naphthylamide (BANA) test. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), and tumor necrosis factor alpha (TNF-alpha) levels were measured in all participants. Assessments of risk factors associated with elevated levels of markers of systemic inflammation were also determined. Multiple regression analysis was employed to analyze the data.IL-6 levels were significantly higher in participants with more-extensive periodontal disease than in other participants. Periodontal disease extent was significantly associated with higher TNF-alpha plasma levels, controlling for established risk factors for elevated TNF-alpha levels. Participants with BANA-positive species had significantly higher CRP plasma levels when controlling for risk factors for elevated CRP levels.Periodontal disease and infection may be modifiable risk indicators for elevated levels of systemic inflammatory markers in older people.

Abstract

Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

Abstract

The metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease; however, no prospective studies have examined the metabolic syndrome as a risk factor for chronic kidney disease (CKD). A total of 10,096 nondiabetic participants who were in the Atherosclerosis Risk in Communities study and had normal baseline kidney function composed the study cohort. The metabolic syndrome was defined according to recent guidelines from the National Cholesterol Education Program. Incident CKD was defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2 at study year 9 among those with an eGFR > or =60 ml/min per 1.73 m2 at baseline. After 9 yr of follow-up, 691 (7%) participants developed CKD. The multivariable adjusted odds ratio (OR) of developing CKD in participants with the metabolic syndrome was 1.43 (95% confidence interval [CI], 1.18 to 1.73). Compared with participants with no traits of the metabolic syndrome, those with one, two, three, four, or five traits of the metabolic syndrome had OR of CKD of 1.13 (95% CI, 0.89 to 1.45), 1.53 (95% CI, 1.18 to 1.98), 1.75 (95% CI, 1.32 to 2.33), 1.84 (95% CI, 1.27 to 2.67), and 2.45 (95% CI, 1.32 to 4.54), respectively. After adjusting for the subsequent development of diabetes and hypertension during the 9 yr of follow-up, the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51). The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults.

Abstract

Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increased risk for morbidity and mortality, independent of the time-averaged concentration of urea. Observational studies of dialysis session length have yielded conflicting results, although virtually all studies have confounded hemodialysis session length with hemodialysis efficiency or dose. Limited observational data from nocturnal hemodialysis programs more strongly suggest an independent beneficial effect of longer session length. In aggregate, data on the effects of hemodialysis session length are inconclusive. Future studies should evaluate hemodialysis session length independent of efficiency, and should consider the evaluation of dose by using other clearance parameters and the adequacy of ultrafiltration in addition to solute kinetics.

Abstract

Although depression and dialysis withdrawal are relatively common among individuals with ESRD, there have been few systematic studies of suicide in this population. The goals of this study were to compare the incidence of suicide with national rates and to contrast the factors associated with suicide with those associated with withdrawal in persons with ESRD. All individuals who were aged 15 yr and older and initiated dialysis between April 1, 1995, and November 30, 2000, composed the analytic cohort. Patients were censored at the time of death, transplantation, or October 31, 2001. Death as a result of suicide in the ESRD population and the general US population was ascertained from the Death Notification Form and the Centers for Disease Control and Prevention, respectively. Standardized incidence ratios for suicide among patient subgroups were computed using national data from the year 2000 as the reference population. The crude suicide rate from 1995 to 2001 was 24.2 suicides per 100,000 patient-years, and the overall standardized incidence ratio for suicide was 1.84 (95% confidence interval, 1.50 to 2.27). In multivariable models, age > or =75 yr, male gender, white or Asian race, geographic region, alcohol or drug dependence, and recent hospitalization with mental illness were significant independent predictors of death as a result of suicide. Persons with ESRD are significantly more likely to commit suicide than persons in the general population. Although relatively rare, risk assessment can be used to identify patients for whom counseling and other interventions might be beneficial.

Abstract

Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.

Abstract

Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease.We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep.Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01).Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

Abstract

Although end-stage renal disease has been associated with cognitive impairment, the relation between lesser degrees of chronic kidney disease (CKD) and cognitive impairment is less well understood.Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed. All participants were younger than 80 years and had established coronary artery disease at study entry. Participants underwent 6 standard tests of cognitive function evaluating various domains. Unadjusted, residual age- and race-adjusted, and multivariable-adjusted linear and logistic regression models were used. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFRs, CKD was categorized as mild (estimated GFR [eGFR], 45 to 60 mL/min/1.73 m2), moderate (eGFR, 30 to 44 mL/min/1.73 m2), and severe (eGFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean eGFR was 57 +/- 14 mL/min/1.73 m2. In multivariable analyses, eGFR was associated significantly with impairment in global cognition, executive function, language, and memory (approximately 15% to 25% increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR). Associations among eGFR and cognitive function were independent of residual effects of age and race (2 key determinants of GFR) and the contributions of education, lifestyle factors, stroke, diabetes, and other laboratory variables.CKD is associated with cognitive impairment in menopausal women with coronary artery disease.

Abstract

Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease.We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves.Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores.The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

Abstract

To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.Cross-sectional study.University-affiliated ambulatory nephrology and dialysis practices.Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3.Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation.There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P

Abstract

Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown.To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function.CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

Abstract

Moderate to severe pain frequently accompanies chronic diseases in general and end-stage renal disease (ESRD) in particular. Several analgesic agents and associated metabolites show altered pharmacokinetics in the presence of reduced glomerular filtration rate. Drug-related side effects may exacerbate symptoms frequently observed in persons with chronic kidney disease (CKD; eg, fatigue, nausea, vomiting, and constipation) or those often attributed to hemodialysis therapy (eg, orthostatic hypotension and impaired cognition). Persons with advanced CKD and ESRD are at increased risk for adverse effects of analgesic agents because of enhanced drug sensitivity, comorbid conditions, and concurrent medication use. Dose adjustment and avoidance of certain analgesics may be required in patients with advanced CKD and ESRD. We review the available evidence on pharmacokinetics and adverse drug effects of various analgesic agents commonly used in patients with advanced CKD and ESRD. Determining an optimal approach to the control of pain in patients with advanced CKD and ESRD will require additional research.

Abstract

In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.

Abstract

Although acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality, its molecular basis remains incompletely defined. The present study examined global gene expression in the well-characterized ischemia-reperfusion model of ARF using DNA microarray technology.Male Wistar rats underwent bilateral renal ischemia (30 min) or sham operation, followed by reperfusion for 1, 2, 3 or 4 days. Plasma creatinine increased approximately fivefold over baseline, peaking on day 1. Renal total RNA was used to probe cDNA microarrays.Alterations in expression of 18 genes were identified by microarray analysis. Nine genes were up-regulated (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1, fibronectin, heat-responsive protein 12 and FK506 binding protein in the established phase), whereas another nine were down-regulated (glutamine synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14, Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established phase). The identities of these 18 genes were sequence-verified. Changes in gene expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and PPARgamma have not previously been known to be involved in ARF.Using DNA microarray technology, we identified changes in expression of 18 genes during renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR. Several genes, not previously been identified as playing a role in ischemic ARF, may have importance in this disease.

Abstract

DNA microarrays, or gene chips, allow surveys of gene expression, (i.e., mRNA expression) in a highly parallel and comprehensive manner. The pattern of gene expression produced, known as the expression profile, depicts the subset of gene transcripts expressed in a cell or tissue. At its most fundamental level, the expression profile can address qualitatively which genes are expressed in disease states. However, with the aid of bioinformatics tools such as cluster analysis, self-organizing maps, and principle component analysis, more sophisticated questions can be answered. Microarrays can be used to characterize the functions of novel genes, identify genes in a biologic pathway, analyze genetic variation, and identify therapeutic drug targets. Moreover, the expression profile can be used as a tissue or disease "fingerprint." This review details the fabrication of arrays, data management tools, and applications of microarrays to the field of renal research and the future of clinical practice.